Category: OSCPP

Evaluate the mutagenic potential of a test article based on the reversion of selective growth mutations

OBJECTIVE:

The purpose of this study is to evaluate the mutagenic potential of a test article based on the reversion of selective growth mutations in several strains of Salmonella typhimurium bacteria and in Escherichia coli WP2 uvrA bacteria, in the presence and absence of S9 activation. This protocol is based on OECD Guideline for Testing of Chemicals: No. 471 – Bacterial Reverse Mutation Test and U.S. EPA Health Effects Test Guidelines OSCPP/OPPTS 870.5100 – Bacterial Reverse mutation Test. MB Research Labs utilizes the test guideline recommended bacterial strains (E. coli WP2 uvrA , S. typhimurium TA97a, S. typhimurium TA98, S. typhimurium TA100, and S. typhimurium TA1535). More information available here.

Basis of the Method:

The test system will be exposed to the test article via the plate incorporation method, which has been shown to effectively detect a wide variety of mutagenic compounds. This assay is based on the methodology originally described by Ames, et al. (1975) and updated by Maron and Ames (1983) and complies with the Guidelines.

Data Interpretation:

In general, a 2-fold increase with or without metabolic activation will be considered a positive response. Dose-related increases approaching a 2-fold increase will be deemed equivocal and a repeat test will be recommended.

Negative Results will be determined by the absence of a dose-related increase in all five tester strains, again taking into account toxicity of the test article as well as the quality checks of the assay.

Positive Results from the bacterial reverse mutation test indicate that the substance induces point mutations by base substitutions or frame shifts in the genome of either Salmonella typhimurium and/or Escherichia coli. Negative results indicate that under the test conditions, the test substance is not mutagenic in the tested species.

This study is conducted in accordance with the Good Laboratory Practices of the EPA, 40 CFR 160 and 792, FDA 21 CFR Part 58, and as specified in the OECD, Principles on Good Laboratory Practice, revised 1997.